Disease relevance of protirelin

• If the clinical presentation was not characteristic of hyperthyroidism or if the FT3I was not elevated, a thyrotropin-releasing hormone (TRH) test was performed [1].
• Transcription from the TRH promoter was regulated in a physiologically faithful manner, being significantly increased in hypothyroidism and decreased in T3-treated animals [2].
• Lymphocytic thyroiditis was not accompanied by any consistent changes in serum T4, T3, and TSH concentrations or in the serum TSH response to thyrotropin-releasing hormone (TRH) suggesting that the thyroiditis was not of sufficient severity or duration to induce primary thyroid gland failure [3].
• Normal menstrual function was restored after surgical removal of the "stone," and galactorrhea subsided although the prolactin response to thyrotropin-releasing hormone (TRH) remained abnormal [4].
• The thyroid-stimulating hormone (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH), administered during the follicular and luteal phases of the menstrual cycle, were examined in 14 women with prospectively confirmed premenstrual syndrome and in nine control subjects [5].

Psychiatry related information on protirelin

• Abnormal anterior pituitary (AP) responsiveness to acute administration of thyrotropin-releasing hormone (TRH) and luteinizing hormone-follicle stimulating hormone-releasing hormone (LH-RH) was investigated in 14 patients (two men and 12 women) suffering from primary affective disorders [6].
• The authors evaluated DST and TRH test results in 29 depressed hospitalized patients; both tests significantly discriminated patients with nonendogenous depression from those with endogenous depression [7].
• Thyrotropin-releasing hormone (TRH) and Alzheimer's disease [8].
• The authors studied the TSH and prolactin responses to a standard 500-micrograms thyrotropin-releasing hormone (TRH) stimulation test in 12 patients with panic disorder and 10 control subjects [9].
• The thyrotropin-releasing hormone (TRH) stimulation test and the dexamethasone suppression test (DST) were administered to 21 patients with schizophreniform disorder at the time of admission for acute illness: 9 showed dysregulation on one or the other test [10].

High impact information on protirelin

• Conversion of PtdIns to polyphosphoinositides and TRH (and GTP)-activated phosphoinositide hydrolysis are known to occur in plasma membrane isolated from GH3 cells [11].
• We report here that thyrotropin-releasing hormone (TRH) acts within the CNS to elicit a vagus-dependent stimulation of gastric acid secretion [12].
• This report describes studies with nerve endings isolated from the rat hypothalamus in which dopamine at higher concentrations than those used previously has been found to stimulate the degradation of LH-RH but not thyrotropin releasing hormone (TRH) [13].
• Small intestine epithelial cells were found to express receptors for thyrotropin-releasing hormone (TRH) and to be a primary source of intestine-derived thyroid-stimulating hormone (TSH) [14].
• Thyroid hormone regulates TRH biosynthesis in the paraventricular nucleus of the rat hypothalamus [15].

Chemical compound and disease context of protirelin

• All were considered to have hypothalamic hypothyroidism on the basis of low thyroxine (T4) concentrations, inappropriately low thyrotropin (TSH) levels, with a normal TSH response to thyrotropin-releasing hormone (TRH, 500 microgram intravenously) in three, and absence of a pituitary lesion [16].
• Comparison of thyrotropin-releasing hormone (TRH), naloxone, and dexamethasone treatments in experimental spinal injury [17].
• Suppression by thyrotropin-releasing hormone (TRH) of growth hormone release induced by arginine and insulin-induced hypoglycemia in man [18].
• The psychopathological correlates of increased post-dexamethasone cortisol and decreased thyroid stimulating hormone (TSH) responsivity to TRH were middle and delayed insomnia and weight loss [19].
• Imidazole-substituted analogues of TRH limit behavioral deficits after experimental brain trauma [20].

Biological context of protirelin

• Thyrotropin-releasing hormone (TRH), however, causes a slow downregulation of TRH receptors (TRH-Rs), with a half-time of approximately 12 hours, in GH3 rat pituitary cells [21].
• In addition, PAMase activity is able to generate TRH when incubated with less than Glu-His-Pro-Gly, a tetrapeptide present as a repetitive sequence in the TRH precursor [22].
• On the neuropharmacology of thyrotropin releasing hormone (TRH) [23].
• A mutant Galpha16 with four consensus PKC phosphorylation sites removed is not phosphorylated in vivo, and TRH responses mediated through the mutant are not regulated by PKC [24].
• These data suggest that TRH specifically enhances the in vitro antibody response via production of immunoreactive TSH [25].

Anatomical context of protirelin

• The mechanism of TRH-R downregulation was studied by monitoring TRH-evoked depolarizing currents in Xenopus oocytes injected with GH3 cell RNA as a bioassay for TRH-R messenger RNA (mRNA) activity [21].
• All controls but not patient before thyroxine was started had a normal thyroid response to thyroid stimulating hormone (TSH), circulating concentrations of which were increased by administration of 500 micrograms thyrotropin releasing hormone (TRH) [26].
• CONCLUSIONS: Cerebral TRH inhibits canine gallbladder contraction by stimulation of vagal outflow and subsequent release of VIP acting via its specific receptor whereas cerebral CGRP inhibits gallbladder contraction by stimulation of sympathetic, noradrenergic outflow via alpha-adrenergic receptors [27].
• The perinatal evolution of the TRH precursor levels in the pancreas is similar to that of PAMase activity (unpublished results) [22].
• A significant fraction of this activity is contained in the beta cells of the islets of Langerhans and is colocalized with thyrotropin-releasing hormone (TRH) and its precursor in secretory granules [22].

Associations of protirelin with other chemical compounds

• The responsiveness on the two hemispheres to TRH and AcCho in mRNA-injected oocytes is opposite to that for the common intrinsic AcCho response in that there is a much greater response when agonist is applied at the animal rather than the vegetal hemisphere [28].
• Strong stimulation of either Ca(2+) entry (by depolarization with high K(+) or acethylcholine) or Ca(2+) release from the intracellular Ca(2+) stores (by stimulation with caffeine, UTP, bradykinin, or thyrotropin-releasing hormone (TRH)) produced similar Ca(2+) signals in cytosol and nucleus [29].
• These data indicate that dexamethasone a) suppresses TSH secretion without increasing fT3 and fT4 and b) blunts the TSH, but not the PRL response, to TRH [30].
• Paradoxical responsiveness of adrenocorticotropin and cortisol to thyrotropin releasing hormone (TRH) in pregnant women. Evidence for intermediate lobe activity [31]?
• Similar to its effect on TRH modulation of I(K), lidocaine (100 microM) attenuated the inhibition of Ca++ channels in GH3 cells by somatostatin (1 microM) [32].

Gene context of protirelin

• As a result of these studies, experiments were designed to examine the possible immunoregulatory function of thyrotropin-releasing hormone (TRH) on the in vitro antibody response to the T cell-independent Ag BA-TNP [25].
• Thus, several putative seizure-induced anticonvulsant adaptations, such as increases in GABAA receptors and TRH and NPY mRNA fail to occur in tolerant animals [33].
• This enhancement effect by TRH was specifically blocked by rabbit antisera to the TSH-beta subunit, whereas addition of normal rabbit sera had no effect [25].
• Regulation by thyrotropin-releasing hormone (TRH) of TRH receptor mRNA degradation in rat pituitary GH3 cells [34].
• Basal and postdexamethasone levels were measured in 27 patients, and levels after thyrotropin-releasing hormone (TRH) stimulation (delta PRL) were measured in 22 patients [35].

Analytical, diagnostic and therapeutic context of protirelin

• Truncal vagotomy prevented the central inhibitory action of TRH but not that of CGRP, whereas noradrenergic blockade prevented the central inhibitory action of CGRP but not that of TRH [27].
• In the third patient, TSH response to TRH went from subnormal to normal after treatment with growth hormone and thyroxine [36].
• Thyrotropin-releasing hormone (TRH) receptors. Localization by light microscopic autoradiography in rat brain using [3H][3-Me-His2]TRH as the radioligand [37].
• A low dose (0.5 mg) of thyrotropin-releasing hormone (TRH), a short-acting tripeptide with known analeptic properties, was administered to eight depressed patients 5 minutes after ECT session 3 or 4 in a double-blind, placebo-controlled crossover design [38].
• The purpose of this study was to evaluate whether or not the administration of the dexamethasone suppression test (DST) and TRH test in depressed patients, just before their entering clinical trials, has any impact on their symptoms [39].

References